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J Nucl Med. 2008; 49 (Supplement 1):289P
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Radiopharmaceutical Chemistry: New Chemistry-Oncology

New Chemistry-Oncology Posters

Biodistribution of [11]MDDI in normal and tumor-bearing rats

Yoshinori Miyake1, Hiroshi Watabe2, Youichirou Ohta2, Yuji Kuge3, Noboru Teramoto2, Yoshio Ishida1, Hideo Saji4 and Hidehiro Iida2

1 Nuclear Medicine & Radiology, National Cardiovascular Center, Suita, Osaka, Japan; 2 Investigative Radiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan; 3 Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 4 Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Kyoto, Japan

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Objectives: Poly (ADP-ribose) polymerse (PARP) is a nuclear enzyme involved in a variety of physiological events and significantly increases cancers. To evaluate whether it is possible to image an activation of PARP with PET, we investigated the uptake of [11C]MDDI, a potent PARP inhibitor, in the normal and tumor of rats.

Methods: Normally male Sprague-Dawley (SD) rats (n=4) and male SD rats (n=2) inoculated with allogenic breast cancer cells (MRMT-1) into the right thigh were used. [11C]MDDI (70-79 MBq/ a rat) was administrated into the tail vein. Dynamic scanning with animal PET was started at the time of [11C]MDDI injection. The normal rats were sacrificed at 30 min post-injection and then the organs were excised. The tissue uptakes were evaluated by percent injection dose /g tissue (%ID/g). For rats with tumor, region of interests (ROIs) were placed on the tumor and reference regions in the left thigh, respectively.

Results: The %ID/g values was highest in the liver (0.573 ± 0.141 %), followed by the kidney (0.237 ± 0.04%), spleen (0.132 ± 0.025 %), and heart (0.116 ± 0.032 %), blood (0.108 ± 0.029 %) in decreasing order. The uptake of the radiotracer in the tumor increased rapidly and then the uptake level was retained from 12 min post-injection of the radiotracer in the kinetic studies of [11C]MDDI by PET and the tumor/reference ratio was 1.64.

Conclusions: [11C]MDDI was rapidly incorporated into and retained in the tumor. [11C]MDDI may enable positive detection of PARP activity in tumor by PET.





This Article
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Right arrow Articles by Iida, H.